Atenolol {or 4-[2-hydroxy-3-(isopropylamino)propoxy]phenylacetamide} crystallizes with 4-aminobenzoic acid to give the salt {3-[4-(aminocarbonylmethyl)phenoxy]-2-hydroxypropyl}isopropylammonium 4-aminobenzoate monohydrate, C14H23N2O3+·C7H6NO2-·H2O. In the crystal structure, the water molecule, the carboxylate group of 4-aminobenzoate, and the hydroxy and ether O atoms of atenolol form a supramolecular R33(11) heterosynthon. Three other types of supramolecular synthons link the asymmetric unit into a two-dimensional structure.
Supporting information
CCDC reference: 672543
A mixture of atenolol (0.067 g, 0.25 mmol) and 4-aminobenzoic acid (0.034 g,
0.25 mmol) was dissolved in ethanol (95%) (15 ml). The solution was kept in
air and after several days colorless crystals were obtained. Differential
scanning calorimetry showed two endothermic peaks, at 395 and 434 K.
The structure was solved by direct methods. All non-H atoms were refined with
anisotropic displacement parameters. H atoms bonded to C atoms were positioned
geometrically and treated as riding [C—H = 0.95–1.00 Å, with
Uiso(H) = 1.2Ueq(C) or 1.5Ueq(C)]. H atoms bonded
to N and O were located in difference maps and were refined with a distance
restraint of O—H = N—H = 0.86 (1) Å. The displacement parameters were
freely refined. The maximum residual electron density is larger than normally
expected. The nearest atom to this maximum is atom C10 at a distance of 1.15 Å.
Data collection: COLLECT (Nonius, 1999); cell refinement: HKL SCALEPACK (Otwinowski & Minor, 1997); data reduction: HKL DENZO and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: X-SEED (Barbour, 2001); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).
{3-[4-(aminocarbonylmethyl)phenoxy]-2-hydroxypropyl)isopropylammonium
4-aminobenzoate monohydrate
top
Crystal data top
C14H23N2O3+·C7H6NO2−·H2O | F(000) = 1808 |
Mr = 421.49 | Dx = 1.313 Mg m−3 |
Monoclinic, C2/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -C2yc | Cell parameters from 31999 reflections |
a = 28.547 (6) Å | θ = 2.6–27.5° |
b = 7.4223 (15) Å | µ = 0.10 mm−1 |
c = 23.822 (5) Å | T = 150 K |
β = 122.34 (3)° | Prism, colorless |
V = 4265 (2) Å3 | 0.48 × 0.20 × 0.16 mm |
Z = 8 | |
Data collection top
Nonius KappaCCD diffractometer | 3926 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.021 |
Graphite monochromator | θmax = 27.5°, θmin = 2.9° |
Detector resolution: 9 pixels mm-1 | h = −36→36 |
CCD scans | k = −8→9 |
8459 measured reflections | l = −30→30 |
4897 independent reflections | |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.048 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.138 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.08 | w = 1/[σ2(Fo2) + (0.0684P)2 + 3.821P] where P = (Fo2 + 2Fc2)/3 |
4897 reflections | (Δ/σ)max < 0.001 |
309 parameters | Δρmax = 0.66 e Å−3 |
9 restraints | Δρmin = −0.28 e Å−3 |
Crystal data top
C14H23N2O3+·C7H6NO2−·H2O | V = 4265 (2) Å3 |
Mr = 421.49 | Z = 8 |
Monoclinic, C2/c | Mo Kα radiation |
a = 28.547 (6) Å | µ = 0.10 mm−1 |
b = 7.4223 (15) Å | T = 150 K |
c = 23.822 (5) Å | 0.48 × 0.20 × 0.16 mm |
β = 122.34 (3)° | |
Data collection top
Nonius KappaCCD diffractometer | 3926 reflections with I > 2σ(I) |
8459 measured reflections | Rint = 0.021 |
4897 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.048 | 9 restraints |
wR(F2) = 0.138 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.08 | Δρmax = 0.66 e Å−3 |
4897 reflections | Δρmin = −0.28 e Å−3 |
309 parameters | |
Special details top
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell e.s.d.'s are taken
into account individually in the estimation of e.s.d.'s in distances, angles
and torsion angles; correlations between e.s.d.'s in cell parameters are only
used when they are defined by crystal symmetry. An approximate (isotropic)
treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s.
planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor
wR and goodness of fit S are based on F2, conventional
R-factors R are based on F, with F set to zero for
negative F2. The threshold expression of F2 >
σ(F2) is used only for calculating R-factors(gt) etc.
and is not relevant to the choice of reflections for refinement.
R-factors based on F2 are statistically about twice as large
as those based on F, and R- factors based on ALL data will be
even larger. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O1 | 0.73138 (5) | 1.06180 (19) | 0.95218 (6) | 0.0379 (3) | |
O2 | 0.57171 (5) | 0.80667 (17) | 0.66372 (5) | 0.0274 (3) | |
O3 | 0.50747 (5) | 0.65977 (16) | 0.54222 (6) | 0.0256 (3) | |
H3 | 0.4804 (8) | 0.697 (4) | 0.5025 (7) | 0.070 (8)* | |
O4 | 0.37605 (5) | 0.87151 (18) | 0.45027 (6) | 0.0327 (3) | |
O5 | 0.43244 (5) | 0.75400 (17) | 0.42186 (6) | 0.0295 (3) | |
O6 | 0.45848 (5) | 0.97970 (16) | 0.57502 (6) | 0.0281 (3) | |
H6A | 0.4876 (7) | 0.913 (3) | 0.5921 (12) | 0.058 (7)* | |
H6B | 0.4339 (8) | 0.934 (3) | 0.5368 (7) | 0.056 (7)* | |
N1 | 0.70651 (6) | 1.0551 (2) | 1.02724 (7) | 0.0314 (3) | |
H1A | 0.7251 (8) | 1.154 (2) | 1.0446 (11) | 0.043 (6)* | |
H1B | 0.6844 (8) | 1.008 (3) | 1.0379 (11) | 0.039 (6)* | |
N2 | 0.54407 (6) | 0.65511 (19) | 0.45103 (7) | 0.0222 (3) | |
H8 | 0.5382 (8) | 0.7656 (15) | 0.4369 (9) | 0.032 (5)* | |
H9 | 0.5137 (6) | 0.608 (3) | 0.4443 (10) | 0.033 (5)* | |
N3 | 0.22681 (6) | 0.9619 (2) | 0.13403 (7) | 0.0321 (3) | |
H3A | 0.2401 (8) | 0.967 (3) | 0.1088 (9) | 0.034 (5)* | |
H3B | 0.2034 (8) | 1.046 (2) | 0.1274 (11) | 0.041 (6)* | |
C1 | 0.70517 (7) | 0.9912 (2) | 0.97382 (8) | 0.0261 (3) | |
C2 | 0.67087 (7) | 0.8208 (2) | 0.94343 (8) | 0.0261 (3) | |
H2A | 0.6950 | 0.7144 | 0.9646 | 0.031* | |
H2B | 0.6412 | 0.8169 | 0.9532 | 0.031* | |
C3 | 0.64480 (6) | 0.8094 (2) | 0.86914 (8) | 0.0233 (3) | |
C4 | 0.59326 (7) | 0.8875 (2) | 0.82566 (8) | 0.0280 (4) | |
H4 | 0.5739 | 0.9448 | 0.8431 | 0.034* | |
C5 | 0.56977 (7) | 0.8832 (2) | 0.75769 (8) | 0.0282 (4) | |
H5 | 0.5347 | 0.9377 | 0.7288 | 0.034* | |
C6 | 0.67132 (6) | 0.7238 (2) | 0.84205 (8) | 0.0251 (3) | |
H6 | 0.7063 | 0.6685 | 0.8709 | 0.030* | |
C7 | 0.64824 (6) | 0.7166 (2) | 0.77379 (8) | 0.0251 (3) | |
H7 | 0.6670 | 0.6559 | 0.7563 | 0.030* | |
C8 | 0.59759 (6) | 0.7990 (2) | 0.73166 (7) | 0.0230 (3) | |
C9 | 0.59748 (6) | 0.7151 (2) | 0.63417 (7) | 0.0222 (3) | |
H9A | 0.6026 | 0.5858 | 0.6463 | 0.027* | |
H9B | 0.6341 | 0.7688 | 0.6492 | 0.027* | |
C10 | 0.55851 (6) | 0.7380 (2) | 0.55980 (7) | 0.0222 (3) | |
H10 | 0.5528 | 0.8695 | 0.5490 | 0.027* | |
C11 | 0.58429 (6) | 0.6518 (2) | 0.52428 (7) | 0.0226 (3) | |
H11A | 0.6183 | 0.7183 | 0.5354 | 0.027* | |
H11B | 0.5948 | 0.5257 | 0.5394 | 0.027* | |
C12 | 0.56114 (7) | 0.5527 (2) | 0.41016 (8) | 0.0263 (4) | |
H12 | 0.5682 | 0.4245 | 0.4255 | 0.032* | |
C13 | 0.61379 (8) | 0.6293 (3) | 0.41884 (10) | 0.0334 (4) | |
H13A | 0.6447 | 0.6106 | 0.4647 | 0.050* | |
H13B | 0.6090 | 0.7586 | 0.4090 | 0.050* | |
H13C | 0.6218 | 0.5683 | 0.3884 | 0.050* | |
C14 | 0.51309 (8) | 0.5568 (3) | 0.33857 (9) | 0.0398 (5) | |
H14A | 0.5064 | 0.6812 | 0.3223 | 0.060* | |
H14B | 0.4798 | 0.5094 | 0.3356 | 0.060* | |
H14C | 0.5220 | 0.4826 | 0.3115 | 0.060* | |
C15 | 0.38704 (6) | 0.8242 (2) | 0.40757 (8) | 0.0232 (3) | |
C16 | 0.34397 (6) | 0.8527 (2) | 0.33539 (8) | 0.0217 (3) | |
C17 | 0.35378 (6) | 0.8016 (2) | 0.28615 (8) | 0.0241 (3) | |
H17 | 0.3876 | 0.7428 | 0.2986 | 0.029* | |
C18 | 0.31528 (7) | 0.8349 (2) | 0.21960 (8) | 0.0255 (3) | |
H18 | 0.3224 | 0.7960 | 0.1868 | 0.031* | |
C19 | 0.29433 (6) | 0.9401 (2) | 0.31583 (8) | 0.0238 (3) | |
H19 | 0.2867 | 0.9750 | 0.3485 | 0.029* | |
C20 | 0.25600 (6) | 0.9771 (2) | 0.24964 (8) | 0.0247 (3) | |
H20 | 0.2226 | 1.0380 | 0.2375 | 0.030* | |
C21 | 0.26583 (6) | 0.9259 (2) | 0.20052 (8) | 0.0247 (3) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0402 (7) | 0.0451 (8) | 0.0357 (7) | −0.0137 (6) | 0.0250 (6) | −0.0130 (6) |
O2 | 0.0247 (6) | 0.0380 (7) | 0.0172 (5) | 0.0050 (5) | 0.0096 (5) | −0.0017 (5) |
O3 | 0.0235 (6) | 0.0281 (6) | 0.0225 (6) | −0.0037 (5) | 0.0106 (5) | −0.0009 (5) |
O4 | 0.0296 (6) | 0.0454 (8) | 0.0232 (6) | −0.0003 (5) | 0.0142 (5) | 0.0016 (5) |
O5 | 0.0239 (6) | 0.0340 (7) | 0.0247 (6) | 0.0044 (5) | 0.0090 (5) | 0.0039 (5) |
O6 | 0.0296 (6) | 0.0281 (6) | 0.0274 (6) | 0.0044 (5) | 0.0158 (5) | 0.0019 (5) |
N1 | 0.0334 (8) | 0.0360 (9) | 0.0223 (7) | 0.0007 (7) | 0.0132 (6) | −0.0052 (6) |
N2 | 0.0231 (7) | 0.0247 (7) | 0.0195 (7) | −0.0029 (5) | 0.0119 (6) | −0.0021 (5) |
N3 | 0.0251 (7) | 0.0450 (9) | 0.0228 (7) | 0.0017 (7) | 0.0106 (6) | 0.0047 (7) |
C1 | 0.0227 (7) | 0.0315 (9) | 0.0197 (7) | 0.0031 (7) | 0.0084 (6) | −0.0025 (7) |
C2 | 0.0269 (8) | 0.0316 (9) | 0.0194 (8) | −0.0001 (7) | 0.0121 (7) | −0.0012 (7) |
C3 | 0.0222 (7) | 0.0262 (8) | 0.0200 (7) | −0.0032 (6) | 0.0103 (6) | −0.0026 (6) |
C4 | 0.0244 (8) | 0.0358 (9) | 0.0252 (8) | 0.0029 (7) | 0.0141 (7) | −0.0044 (7) |
C5 | 0.0205 (7) | 0.0387 (9) | 0.0217 (8) | 0.0048 (7) | 0.0089 (6) | −0.0023 (7) |
C6 | 0.0215 (7) | 0.0295 (8) | 0.0204 (8) | 0.0037 (6) | 0.0085 (6) | −0.0002 (7) |
C7 | 0.0235 (8) | 0.0294 (8) | 0.0229 (8) | 0.0031 (6) | 0.0128 (7) | −0.0029 (7) |
C8 | 0.0210 (7) | 0.0275 (8) | 0.0183 (7) | −0.0023 (6) | 0.0090 (6) | −0.0030 (6) |
C9 | 0.0227 (7) | 0.0254 (8) | 0.0189 (7) | −0.0025 (6) | 0.0114 (6) | −0.0036 (6) |
C10 | 0.0221 (7) | 0.0250 (8) | 0.0190 (7) | −0.0023 (6) | 0.0105 (6) | −0.0005 (6) |
C11 | 0.0231 (7) | 0.0252 (8) | 0.0166 (7) | −0.0009 (6) | 0.0088 (6) | 0.0004 (6) |
C12 | 0.0355 (9) | 0.0232 (8) | 0.0263 (8) | −0.0029 (7) | 0.0206 (7) | −0.0041 (7) |
C13 | 0.0369 (9) | 0.0347 (9) | 0.0373 (10) | −0.0009 (8) | 0.0255 (8) | −0.0047 (8) |
C14 | 0.0437 (11) | 0.0518 (12) | 0.0258 (9) | −0.0092 (9) | 0.0198 (8) | −0.0098 (9) |
C15 | 0.0228 (7) | 0.0214 (7) | 0.0229 (8) | −0.0045 (6) | 0.0106 (6) | 0.0022 (6) |
C16 | 0.0201 (7) | 0.0215 (7) | 0.0224 (8) | −0.0035 (6) | 0.0106 (6) | 0.0011 (6) |
C17 | 0.0205 (7) | 0.0246 (8) | 0.0281 (8) | 0.0002 (6) | 0.0136 (7) | 0.0012 (7) |
C18 | 0.0264 (8) | 0.0288 (8) | 0.0236 (8) | −0.0011 (6) | 0.0150 (7) | −0.0003 (7) |
C19 | 0.0243 (8) | 0.0258 (8) | 0.0236 (8) | −0.0025 (6) | 0.0143 (7) | 0.0001 (6) |
C20 | 0.0193 (7) | 0.0280 (8) | 0.0261 (8) | 0.0005 (6) | 0.0116 (6) | 0.0028 (7) |
C21 | 0.0219 (7) | 0.0273 (8) | 0.0229 (8) | −0.0042 (6) | 0.0105 (6) | 0.0010 (6) |
Geometric parameters (Å, º) top
O1—C1 | 1.230 (2) | C6—H6 | 0.9500 |
O2—C8 | 1.3745 (19) | C7—C8 | 1.385 (2) |
O2—C9 | 1.4329 (19) | C7—H7 | 0.9500 |
O3—C10 | 1.4078 (19) | C9—C10 | 1.515 (2) |
O3—H3 | 0.887 (10) | C9—H9A | 0.9900 |
O4—C15 | 1.264 (2) | C9—H9B | 0.9900 |
O5—C15 | 1.263 (2) | C10—C11 | 1.528 (2) |
O6—H6A | 0.862 (10) | C10—H10 | 1.0000 |
O6—H6B | 0.866 (10) | C11—H11A | 0.9900 |
N1—C1 | 1.339 (2) | C11—H11B | 0.9900 |
N1—H1B | 0.868 (10) | C12—C14 | 1.513 (3) |
N1—H1A | 0.868 (10) | C12—C13 | 1.514 (2) |
N2—C11 | 1.490 (2) | C12—H12 | 1.0000 |
N2—C12 | 1.507 (2) | C13—H13A | 0.9800 |
N2—H8 | 0.868 (9) | C13—H13B | 0.9800 |
N2—H9 | 0.866 (9) | C13—H13C | 0.9800 |
N3—C21 | 1.390 (2) | C14—H14A | 0.9800 |
N3—H3A | 0.865 (9) | C14—H14B | 0.9800 |
N3—H3B | 0.866 (10) | C14—H14C | 0.9800 |
C1—C2 | 1.524 (2) | C15—C16 | 1.500 (2) |
C2—C3 | 1.511 (2) | C16—C19 | 1.393 (2) |
C2—H2A | 0.9900 | C16—C17 | 1.396 (2) |
C2—H2B | 0.9900 | C17—C18 | 1.385 (2) |
C3—C6 | 1.384 (2) | C17—H17 | 0.9500 |
C3—C4 | 1.394 (2) | C18—C21 | 1.403 (2) |
C4—C5 | 1.382 (2) | C18—H18 | 0.9500 |
C4—H4 | 0.9500 | C19—C20 | 1.383 (2) |
C5—C8 | 1.390 (2) | C19—H19 | 0.9500 |
C5—H5 | 0.9500 | C20—C21 | 1.394 (2) |
C6—C7 | 1.391 (2) | C20—H20 | 0.9500 |
| | | |
C8—O2—C9 | 117.71 (12) | C9—C10—C11 | 109.30 (13) |
C10—O3—H3 | 111.2 (18) | O3—C10—H10 | 109.1 |
H6A—O6—H6B | 108 (2) | C9—C10—H10 | 109.1 |
C1—N1—H1B | 118.6 (15) | C11—C10—H10 | 109.1 |
C1—N1—H1A | 116.8 (16) | N2—C11—C10 | 110.12 (12) |
H1B—N1—H1A | 124 (2) | N2—C11—H11A | 109.6 |
C11—N2—C12 | 115.81 (13) | C10—C11—H11A | 109.6 |
C11—N2—H8 | 109.8 (14) | N2—C11—H11B | 109.6 |
C12—N2—H8 | 106.7 (13) | C10—C11—H11B | 109.6 |
C11—N2—H9 | 106.2 (14) | H11A—C11—H11B | 108.2 |
C12—N2—H9 | 108.1 (14) | N2—C12—C14 | 107.84 (14) |
H8—N2—H9 | 110.2 (19) | N2—C12—C13 | 111.26 (13) |
C21—N3—H3A | 114.7 (14) | C14—C12—C13 | 112.44 (15) |
C21—N3—H3B | 114.6 (15) | N2—C12—H12 | 108.4 |
H3A—N3—H3B | 115 (2) | C14—C12—H12 | 108.4 |
O1—C1—N1 | 122.19 (17) | C13—C12—H12 | 108.4 |
O1—C1—C2 | 122.31 (15) | C12—C13—H13A | 109.5 |
N1—C1—C2 | 115.45 (15) | C12—C13—H13B | 109.5 |
C3—C2—C1 | 113.05 (14) | H13A—C13—H13B | 109.5 |
C3—C2—H2A | 109.0 | C12—C13—H13C | 109.5 |
C1—C2—H2A | 109.0 | H13A—C13—H13C | 109.5 |
C3—C2—H2B | 109.0 | H13B—C13—H13C | 109.5 |
C1—C2—H2B | 109.0 | C12—C14—H14A | 109.5 |
H2A—C2—H2B | 107.8 | C12—C14—H14B | 109.5 |
C6—C3—C4 | 117.88 (14) | H14A—C14—H14B | 109.5 |
C6—C3—C2 | 121.47 (14) | C12—C14—H14C | 109.5 |
C4—C3—C2 | 120.65 (15) | H14A—C14—H14C | 109.5 |
C5—C4—C3 | 121.24 (15) | H14B—C14—H14C | 109.5 |
C5—C4—H4 | 119.4 | O5—C15—O4 | 123.95 (15) |
C3—C4—H4 | 119.4 | O5—C15—C16 | 117.42 (14) |
C4—C5—C8 | 119.86 (15) | O4—C15—C16 | 118.63 (14) |
C4—C5—H5 | 120.1 | C19—C16—C17 | 118.08 (14) |
C8—C5—H5 | 120.1 | C19—C16—C15 | 120.82 (14) |
C3—C6—C7 | 121.84 (15) | C17—C16—C15 | 121.00 (14) |
C3—C6—H6 | 119.1 | C18—C17—C16 | 121.36 (15) |
C7—C6—H6 | 119.1 | C18—C17—H17 | 119.3 |
C8—C7—C6 | 119.21 (15) | C16—C17—H17 | 119.3 |
C8—C7—H7 | 120.4 | C17—C18—C21 | 120.09 (15) |
C6—C7—H7 | 120.4 | C17—C18—H18 | 120.0 |
O2—C8—C7 | 124.51 (14) | C21—C18—H18 | 120.0 |
O2—C8—C5 | 115.53 (14) | C20—C19—C16 | 121.13 (15) |
C7—C8—C5 | 119.95 (15) | C20—C19—H19 | 119.4 |
O2—C9—C10 | 105.80 (12) | C16—C19—H19 | 119.4 |
O2—C9—H9A | 110.6 | C19—C20—C21 | 120.72 (15) |
C10—C9—H9A | 110.6 | C19—C20—H20 | 119.6 |
O2—C9—H9B | 110.6 | C21—C20—H20 | 119.6 |
C10—C9—H9B | 110.6 | N3—C21—C20 | 120.36 (15) |
H9A—C9—H9B | 108.7 | N3—C21—C18 | 121.04 (15) |
O3—C10—C9 | 107.30 (12) | C20—C21—C18 | 118.59 (15) |
O3—C10—C11 | 113.01 (13) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O6—H6A···O2 | 0.86 (1) | 2.22 (1) | 3.042 (2) | 161 (2) |
O6—H6B···O4 | 0.87 (1) | 1.89 (1) | 2.744 (2) | 171 (3) |
O3—H3···O5 | 0.89 (1) | 1.71 (1) | 2.5937 (19) | 172 (3) |
N1—H1B···O4i | 0.87 (1) | 2.15 (1) | 3.008 (2) | 171 (2) |
N3—H3A···O1ii | 0.87 (1) | 2.02 (1) | 2.880 (2) | 171 (2) |
N2—H8···O6ii | 0.87 (1) | 1.92 (1) | 2.7729 (19) | 166 (2) |
N2—H9···O3iii | 0.87 (1) | 2.15 (2) | 2.8120 (19) | 133 (2) |
Symmetry codes: (i) −x+1, y, −z+3/2; (ii) −x+1, −y+2, −z+1; (iii) −x+1, −y+1, −z+1. |
Experimental details
Crystal data |
Chemical formula | C14H23N2O3+·C7H6NO2−·H2O |
Mr | 421.49 |
Crystal system, space group | Monoclinic, C2/c |
Temperature (K) | 150 |
a, b, c (Å) | 28.547 (6), 7.4223 (15), 23.822 (5) |
β (°) | 122.34 (3) |
V (Å3) | 4265 (2) |
Z | 8 |
Radiation type | Mo Kα |
µ (mm−1) | 0.10 |
Crystal size (mm) | 0.48 × 0.20 × 0.16 |
|
Data collection |
Diffractometer | Nonius KappaCCD diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 8459, 4897, 3926 |
Rint | 0.021 |
(sin θ/λ)max (Å−1) | 0.650 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.048, 0.138, 1.08 |
No. of reflections | 4897 |
No. of parameters | 309 |
No. of restraints | 9 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.66, −0.28 |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O6—H6A···O2 | 0.862 (10) | 2.216 (13) | 3.042 (2) | 161 (2) |
O6—H6B···O4 | 0.866 (10) | 1.885 (11) | 2.744 (2) | 171 (3) |
O3—H3···O5 | 0.887 (10) | 1.712 (11) | 2.5937 (19) | 172 (3) |
N1—H1B···O4i | 0.868 (10) | 2.147 (10) | 3.008 (2) | 171 (2) |
N3—H3A···O1ii | 0.865 (9) | 2.022 (10) | 2.880 (2) | 171 (2) |
N2—H8···O6ii | 0.868 (9) | 1.921 (11) | 2.7729 (19) | 166 (2) |
N2—H9···O3iii | 0.866 (9) | 2.150 (17) | 2.8120 (19) | 132.9 (18) |
Symmetry codes: (i) −x+1, y, −z+3/2; (ii) −x+1, −y+2, −z+1; (iii) −x+1, −y+1, −z+1. |
Multicomponent crystals of active pharmaceutical ingredients (APIs) may offer advantages over the corresponding APIs in terms of physical properties such as crystallinity, solubility and dissolution rate (Black et al., 2007; Childs et al., 2007). Hydrogen-bonded supramolecular synthons are commonly used as a reliable method in the formation of these crystals (Wenger & Bernstein, 2006). Recently, the hierarchy of synthons in a competitive environment has been intensively studied (Bis et al., 2007). Atenolol, 4-[2-hydroxy-(3-isopropylaminomethyl)propoxy]phenylacetamide, is a drug belonging to the group of beta blockers used primarily in cardiovascular diseases. From the viewpoint of crystal engineering, atenolol can provide various hydrogen-bonding interactions since it contains multiple typical hydrogen-bonding groups. Recently, Cai et al. (2006) reported its hydrated succinate and fumarate salts, in which various hydrogen bonds result in three-dimensional structures. In this study, we chose 4-aminobenzoic acid as a second component containing both amino and carboxylic acid groups in the structure and prepared the monohydrous molecular salt of atenolol, (I), in which versatile hydrogen-bonding interactions result in a two-dimensional structure.
The crystal structure of (I) contains one atenolol, one 4-aminobenzoic acid and one water molecule in the asymmetric unit. Difference Fourier maps show that 4-aminobenzoic acid transfers the carboxylic acid H atom to the secondary amine of atenolol. The C—O distances in the carboxylate group of 4-aminobenzoic acid are equal within error margins [1.264 (2) and 1.263 (2) Å, respectively]. The water molecule is simultaneously hydrogen bonded to the carboxylate group of 4-aminobenzoic acid and the ether O atom of atenolol (O6—H6B···O4- and O6—H6A ···O2; Table 1). The hydroxy group of atenolol is also hydrogen bonded to the carboxylate group of 4-aminobenzoic acid (O3—H3···O5-), forming a supramolecular R33(11) heterosynthon (Fig. 1). The amide group of atenolol is hydrogen-bonded to the amine group of another 4-aminobenzoic acid molecule [N3—H3A···O1(1 - x, 2 - y, 1 - z)], which generates a centrosymmetric tetramer based on the R66(38) synthon. Moreover, N2+—H8···O6(1 - x, 2 - y, 1 - z) hydrogen bonds between the water molecule and the protonated secondary amine of atenolol participate in the formation of the tetramer. The tetramer is further linked into a one-dimensional chain structure along the b axis by N2+—H9···O3(1 - x, 1 - y, 1 - z) hydrogen bonds between the hydroxy group and the secondary amine from an adjacent atenolol molecule, generating a self-complementary R22(10) synthon (Fig. 2). The amide group of atenolol is also involved in hydrogen-bonding interactions with the carboxylate group of 4-aminobenzoic acid [N1—H1B···O4(1 - x, y, 3/2 - z)], giving a centrosymmetric R64(26) ring which connects the one-dimensional chain into a two-dimensional structure (Fig. 3).
Atenolol contains an amide group, a secondary amine, and hydroxy and ether O atoms. For such a complicated system, it is difficult to predict reliable supramolecular synthons. In the structure of its succinate salt (Cai et al., 2006), the carboxylate group of succinic acid is simultaneously hydrogen bonded to the hydroxy and secondary amine groups of atenolol, generating a centrosymmetric three-component adduct. There exists a hydrogen-bonded chain of amide groups linking the adduct into a two-dimensional structure, which is further linked into a three-dimensional structure by hydrogen bonds between amide and carboxylate groups, together with hydrogen bonds between hydroxy and secondary amine groups. By contrast, in (I), no hydrogen bonding is formed between the carboxylate group of 4-aminobenzoic acid and the secondary amine of atenolol, although 4-aminobenzoic acid transfers its carboxylic acid H atom to the secondary amine. Moreover, the ether O atom of atenolol also participates in hydrogen-bonding interactions, resulting in the R33(11) synthon. The hydrogen-bonding pattern of the amide group in (I) is also different from that in the succinate salt. The amide group generates two rings, R66(38) and R64(26), with amine and carboxylate groups of 4-aminobenzoic acid, respectively. Thus, atenolol interacts with 4-aminobenzoic acid through three types of featured synthons.
In conclusion, in the structure of (I), the water molecule, the carboxylate group of 4-aminobenzoic acid, and hydroxy and ether O atoms of atenolol form a supramolecular heterosynthon R33(11), while three other types of self-complementary supramolecular synthons, R66(38), R64(26) and R22(10), link the asymmetric unit into a two-dimensional structure.